Mitchell's resignation comes at a critical time for the Middle East, which is embroiled in turmoil, and the Israeli-Palestinian peace process, which has been moribund since last September and is now further complicated by an agreement between Palestinian factions to share power.

Obama will deliver a speech next Thursday at the State Department about his administration's views of developments in the region, ahead of a visit to Washington by Israeli Prime Minister Benjamin Netanyahu. Jordan's King Abdullah II also will travel to Washington next week.

In a telephone interview Friday with the MaineToday Media group in Mitchell's home state, Obama said: "George is by any measure one of the finest public servants our nation has ever had." He did not address the resignation directly but said Mitchell is also "a good friend."

White House spokesman Jay Carney said the administration remains focused on the Middle East peace process.

"The president's commitment remains as firm as it was when he took office," Carney said. "This is a hard issue, an extraordinary hard issue."

Since his appointment on Obama's second full day in office in January 2009, Mitchell, 77, had spent much of his time shuttling among the Israelis, Palestinians and friendly Arab states in a bid to restart long-stalled peace talks that would create an independent Palestinian state. In recent months, particularly after the upheaval in Arab countries that ousted longtime U.S. ally and crucial peace partner Hosni Mubarak from power in Egypt, his activity had slowed markedly.

Nimer Hamad, a senior adviser to Palestinian President Mahmoud Abbas, told the AP that Mitchell's job had been made more difficult by Israeli intransigence.

"Mitchell hasn't been in the region in three months," Hamad said. "Whether he resigns or not, it's clear that Mitchell wasn't in the region because he didn't see the possibility of being a mediator between two sides where one of them is not responsive."

AIPAC, the pro-Israel lobby, issued a statement criticizing Palestinian Authority President Mahmoud Abbas, citing his "unwillingness to negotiate directly with his Israeli counterpart without preconditions." AIPAC also denounced Abbas's secular Fatah movement for singing a reconciliation deal with Hamas, the Islamic militant group that governs the Gaza Strip, rather than make peace with Israel.

Jon Alterman, director of the Middle East program at the Center for Strategic and International Studies, said Mitchell's task held greater hope at the time of his appointment.

"But the way the politics worked out, you have an Israeli government that is very skeptical about the ability of negotiating with the Palestinian Authority," Alterman said. "And you have a Palestinian Authority where the internal politics are increasingly fraught.

"So it's hard to find a political consensus either among the Israelis or the Palestinians to move forward on the kinds of negotiations that George Mitchell was appointed to facilitate."

Mitchell believed his patience would serve him well in the Arab-Israeli conflict and its constant forward and backward steps. Speaking of the Northern Ireland conflict, he once said: "I formed the conviction that there is no such thing as a conflict that can't be ended. Conflicts are created, conducted and sustained by human beings. They can be ended by human beings."

Israeli analyst Yossi Alpher, former director of the Jaffee Center for Strategic Studies at Tel Aviv University, said Mitchell's departure could signal a different approach by the Obama administration.

"His methods just didn't work here," Alpher said. "The Northern Ireland method of listen, listen and listen doesn't work here."

Nabil Shaath, a leading Palestinian negotiator, suggested the resignation was not so much a blow to the peace effort as a reflection of its failure — and that should conditions change, the identity of the mediator was not key.

"Mitchell hadn't received enough support from the U.S. administration to make a breakthrough in the peace process. He is a positive man, he is a great man and he is my friend," Shaath said. "But Mitchell can be replaced when the U.S. administration is ready. There is no possibility for a mediator to work without the needed support and pressure from the administration on Israel."

Mitchell has led a long career as politician, businessman, congressional investigator and international mediator.

Upon being announced as the administration's point man for Mideast negotiations, he recalled his role in producing Northern Ireland's Good Friday peace accord in 1998.

"We had 700 days of failure and one day of success," he said. "For most of the time, progress was nonexistent or very slow."

Mitchell believed his patience would serve him well in the Arab-Israeli conflict and its constant forward and backward steps. Speaking of the Northern Ireland conflict, he added: "I formed the conviction that there is no such thing as a conflict that can't be ended. Conflicts are created, conducted and sustained by human beings. They can be ended by human beings."

Mitchell served in the Senate as a Democrat from Maine from 1980 to 1995, the final six years as majority leader. In 2000-01, he headed a fact-finding committee on Mideast violence that recommended commitments by Israel and the Palestinian Authority to immediately and unconditionally end their fighting. The panel urged a cooling-off period and other steps toward peace, but it did not lead to lasting results.

The April 2001 Mitchell report asked Israel to freeze settlements on the West Bank and urged the Palestinians to prevent gunmen in Palestinian-populated areas from firing on Israeli towns and cities. The settlements, as well as Israeli concern over rocket and other attacks on its soil, remain sticking points today.

Mitchell also led the 2007 investigation into the use of performance-enhancing drugs in major league baseball. Before that, he was chairman of The Walt Disney Co. from 2004-2006.